Case 23

Case 23

HISTORY AND PHYSICAL EXAMINATION

Fever, malaise, and sore throat developed in a 55-year-old woman who was otherwise in excellent health. She was treated with antibiotics and analgesics. Six days later, she first noticed that her legs had “buckled” underneath her. That afternoon, she had difficulty climbing steps and became aware of tingling in both hands. She awoke the next morning and could not stand. She was brought to the hospital and was admitted. Apart from a diuretic for mild hypertension, she was taking no other medications.

On physical examination, the patient was afebrile and in no apparent distress. She had normal vital signs, including blood pressure, pulse, and respiration. Neurologic examination revealed normal mental status and cranial nerves. Motor examination was relevant for weakness of the neck flexors (Medical Research Council [MRC] 4+/5), the proximal pelvic muscles (MRC 3/5), and the shoulder muscles (MRC 4-/5). Distally, she performed much better (5-/5). Deep tendon reflexes were absent throughout. Sensory examination was normal, except for mild impairment of touch and pin sensation in both hands. She was unable to sit or stand independently.

An electrodiagnostic (EDX) examination was performed 3 days after admission and 6 days after the onset of neurologic symptoms. This was repeated later, on the 12th day after admission, which corresponded to day 15 from the onset of neurologic symptoms. Needle electromyography was not performed due to the acute nature of the symptoms.

Please now review the Nerve Conduction Studies tables.

EDX FINDINGS AND INTERPRETATION OF DATA

The first set of nerve conduction studies (NCS), performed on day 6 from the onset of neurologic symptoms, revealed the following:

1. Low amplitude median and borderline radial sensory nerve action potentials (SNAPs), with normal sural SNAP.

2. Low-amplitude distal median, ulnar, and peroneal CMAPs with no definite evidence of proximal conduction blocks. The mean distal CMAP amplitude (all distal CMAP amplitudes obtained, divided by the number of nerves studied) is 2.29 mV, and the mean lower limit of normal (all lower limit values of CMAP amplitudes, divided by the number of nerves studied) is 5.41 mV. Thus, the mean CMAP amplitude is 42% of the lower limit of normal values (2.29/5.41 × 100).

Case 23: Nerve Conduction Studies (First Study, Day 6)

Case 23: Nerve Conduction Studies (Second Study, Day 15)

3. Minimal slowing of distal latencies (in the hands) and moderate slowing of conduction velocities. These values are moderate and do not reach the levels of velocity slowing that is pathognomic of demyelination in the presence of low CMAPs (<70% of the lower limit of normal; see discussion). The lowest conduction velocity obtained is 39 m/s which equals 78% of the lower limit of normal.

4. Absent F waves throughout, except for the peroneal F wave, which is prolonged.

The above findings point to pathology at the spinal roots and the peripheral sensory and motor nerves, manifesting as either axonal loss or distal conduction block (as a cause of low distal CMAPs). Only one criterion of demyelination (absent F waves) is fulfilled. The absent F waves and the sural sparing pattern (i.e., abnormal upper extremity SNAPs with normal sural SNAP) are findings that are highly suggestive of GBS (see discussion).

The second study, done 9 days later (15 days from the onset of neurologic symptoms), revealed that now all hand SNAPs (median, ulnar, and radial) are abnormally low in amplitude or absent. In contrast, the sural SNAP continues to be normal. The slowing of distal latencies now is more pronounced, which fulfills one of the criteria for acquired demyelination. The F waves are still absent, fulfilling a second criterion. However, the velocities are still moderately slowed and there is no confirmed conduction block. Thus, in the second study, two criteria of acquired demyelination are fulfilled (three are required; see discussion), and the sural sparing pattern (i.e., abnormal upper extremity SNAPs with normal sural SNAP) is confirmed. These findings are strong evidence for the diagnosis of GBS.

The prognosis here is fair because of low distal CMAPs, although at no time did the mean CMAP amplitude decrease below 20% of the lower limit of normal. The first study is less helpful because the patient had not reached plateau yet and because time for the completion of wallerian degeneration has not been allowed. The second study, done a week after the patient reached plateau, reveals a mean CMAP of 39% of the lower limit of normal.

In summary, the profile of these NCSs is consistent with an acquired demyelinating polyneuropathy as seen with acute inflammatory demyelinating polyneuropathy (AIDP), the most common type of GBS. The prognosis for recovery is fair due to modest decrease in mean CMAP amplitude. A repeat EMG 3 to 5 weeks after the onset of symptoms was recommended to confirm this prognostic prediction.

DISCUSSION

Rapidly Progressive Quadriparesis: Differential Diagnosis

Quadriparesis progressing over days to weeks is a relatively common neurological presentation. Usually, the history is one of an ascending paresis beginning in the lower limbs and progressing cephalad to trunk and upper limb muscles, and often weakening the respiratory, bulbar, and ocular muscles. Descending weakness, progressing in the opposite direction, may occur but is less common. Causes of nontraumatic rapidly progressive quadriparesis are best discussed using the neuraxis as an anatomical guideline. Since many of the disorders manifesting this presentation are due to lower motor neuron dysfunction, it is useful to use the different elements of the motor unit as a tool in setting a complete differential diagnosis (Table C23-1).

Table C23-1 Causes of Rapidly Progressive Quadriparesis

Muscle Disorders

Dermatomyositis

Rhabdomyolysis (drugs, toxins, exercise, trauma, metabolic myopathies, etc.)

Critical illness myopathy

Muscle Membrane Disorders

Familial periodic paralysis

Secondary hypokalemic paralysis (thyrotoxicosis, malabsorption, barium salt poisoning, or abuse of diuretics, laxatives or licorice)

Neuromuscular Junction Disorders

Myasthenia gravis (myasthenic crisis)

Drug-induced neuromuscular blockade

Organophosphate

Black widow spider

Hypermagnesemia (toxemia of pregnancy treated with parenteral magnesium, magnesium-containing antacids, or cathartics)

Hypophosphatemia (parenteral hyperalimentation, phosphate-bindings antacids, acute alcohol intoxication, and severe respiratory alkalosis)

Peripheral Nerve and/Root Disorders

Guillain-Barré syndrome

Acute intermittent porphyria

Diphtheritic polyneuropathy

Critical illness polyneuropathy

Vasculitic neuropathy

Heavy metal acute poisoning (thallium, arsenic)

Diffuse polyradiculopathy (infectious, neoplastic)

Anterior Horn Cell Disorders

Acute poliomyelitis (wild polio viruses, west Nile virus, enteroviruses)

Spinal Cord Disorders

Transverse myelitis

Cord compression (disc herniation, fracture/dislocation, epidural malignancy)

Cord infarction (anterior spinal artery syndrome)

Brainstem Disorders

Central pontine myelinolysis

Pontine infarct (basilar artery thrombosis)

Adapted from Katirji B, Kaminski HJ, Preston DC et al., eds. Neuromuscular disorders in clinical practice. Boston, MA: Butterworth-Heinemann, 2002.

Certain clinical features and diagnostic studies are useful in establishing the correct diagnosis:

• Distribution and temporal progression of weakness. The neurological examination is most useful during the early phases of these disorders, since most ultimately result in a fairly uniform appearance in the later stages of illness, including severe quadriparesis, hyporeflexia, or areflexia, with or without respiratory failure and bulbar or ocular weakness. A detailed history or observation of the progression and distribution of the weakness is extremely useful in making a correct diagnosis. For example, the first symptom of botulism is often asymmetrical ptosis or double vision, followed rapidly by dysphagia, dysarthria, and, finally, respiratory distress and limb weakness. In contrast, in a typical GBS patient, the symptoms often begin with symmetrical weakness of the legs, imbalance and numbness, followed by trunk and upper limb weakness, which may progress into respiratory failure and, sometimes, facial diplegia or diplopia.

• Deep tendon reflexes. The deep tendon reflexes (DTRs) are among the most important signs in patients with rapidly progressive quadriparesis. In general, disorders of peripheral nerve are often associated with early hyporeflexia, while the DTRs are usually spared in neuromuscular junction disorders and myopathies. However, the DTRs are often absent irrespective of the site of pathology within the motor unit when the weakness becomes very severe. For example, the DTRs in botulism are normal until significant limb weakness develops, while they are often depressed or absent in mildly weak limb(s) early in the course of GBS.

• Symmetry of weakness. Asymmetrical weakness is also an important finding early in the course of illness since many patients go on to generalized symmetrical paralysis. In general, subacute polyneuropathies and myopathies are symmetrical from the outset, while subacute neuromuscular junction disorders, polyradiculopathies, and anterior horn cell diseases are often asymmetrical early in their course. For example, the weakness is often symmetrical from the outset in GBS, polymyositis and periodic paralysis, while ocular, bulbar, and limb muscle weakness is often asymmetrical in botulism, myasthenia gravis, carcinomatous polyradiculopathy, and acute paralytic poliomyelitis. However, there are many exceptions. For example, the weakness in vasculitic neuropathy is often asymmetrical and may be restricted to peripheral nerve distributions (mononeuropathy multiplex), while tick paralysis typically causes a rapid symmetrical quadriparesis.

• Extraocular muscle weakness. Extraocular muscle abnormalities are common in neuromuscular junction disorders, particularly botulism and myasthenia gravis. They are rarely found in polyneuropathies and do not occur in subacute myopathies or anterior horn cell disorders. In contrast to ocular findings, bulbar manifestations, particularly dysphagia, are common to most neuromuscular disorders.

• Sensory manifestations. The presence of sensory symptoms excludes all subacute myopathies, and neuromuscular junction and anterior horn cell disorders, unless accompanied by a peripheral neuropathy, such as in paraneoplastic disorders. Sensory symptoms and signs are very common in polyneuropathies and polyradiculopathies.

• Autonomic findings. Autonomic findings are features common to polyneuropathies, polyradiculopathies, and botulism. These include orthostatic hypotension, tachy- and bradyarrhythmias, ileus, urinary retention or incontinence, and pupillary abnormalities.

• Serum electrolytes. Serum electrolytes are easy to measure and may suggest a specific diagnosis. Serum potassium, magnesium, and phosphorus should be obtained promptly in all patients with rapidly progressive quadriparesis (see Table C23-1). The EKG is usually abnormal with hypokalemia (prolonged QT interval, flat T wave and prominent U wave), and hyperkalemia (peaked T waves).

• Serum creatine kinase. Elevated serum creatine kinase (CK) often suggests a primary muscle disorder. When acute rhabdomyolysis leads to severe weakness, the CK is markedly elevated, reaching up to 1000- to 2000-fold of the normal level. In polymyositis and dermatomyositis presenting with rapid quadriparesis, the CK is often elevated, reaching usually up to 100- to 200-fold the normal value. CK is variably elevated in critical illness myopathy, and may be slightly elevated in GBS and acute paralytic poliomyelitis.

• Cerebrospinal fluid. Abnormalities seen in the cerebrospinal fluid (CSF) are generally supportive of a diagnosis, but not pathognomonic. In general, all myopathies and neuromuscular junction disorders are associated with normal CSF, while the CSF is often abnormal in most subacute peripheral polyneuropathies, polyradiculopathies, and anterior horn cell disorders. Elevated CSF protein is among the most common abnormality seen, followed by pleocytosis. The latter is usually dominated by lymphocytes except in infectious disorders where there is often early polymorphonuclear pleocytosis. CSF glucose is sometimes lowered in infectious, carcinomatous or lymphomatous polyradiculopathies (leptomeningeal disease).

• Electrodiagnostic tests. Nerve conduction studies, repetitive nerve stimulation, and needle EMG are invaluable aids in the diagnosis of patients presenting with acute or subacute quadriparesis. In general, NCSs and repetitive nerve stimulation are more useful than needle EMG in the acute phase of these disorders. Although normal NCSs suggest disorders of muscle, neuromuscular junction, spinal roots, or anterior horn cell, many patients with subacute polyneuropathies might have normal NCSs during the first week or two of illness. CMAP amplitudes may be low in botulism, drug-induced neuromuscular blockade, severe myasthenia gravis, or severe necrotizing myopathies. Sensory nerve action potentials (SNAPs) are usually abnormal in patients with subacute neuropathies, but this may be delayed also.

Clinical Features

Guillain-Barré syndrome (GBS), also known as Landry-Guillain-Barré-Strohl syndrome, is the most common cause of subacute flaccid paralysis in the world. It is a generalized disorder of the peripheral nervous system that is characterized by multiple limb and cranial muscle weakness with areflexia. It has an incidence of slightly less than 2 per 100 000 population. Guillain-Barré syndrome is frequently preceded by a viral or bacterial illness, usually an upper respiratory infection or gastroenteritis.

Typically, GBS develops over the course of a few days. Limb weakness appears simultaneously with a slight tingling and impairment of sensation in the hands and feet. The sensory symptoms are rarely painful while myalgia and back pain are common. Weakness usually ascends from the lower limbs to the upper limbs and, sometimes, to the cranial nerves. Less commonly, the weakness in GBS is descending. Facial weakness occurs in approximately one half of patients, and respiratory failure requiring mechanical ventilation occurs in one-third. Typically, progression lasts up to 4 weeks, while progression exceeding 4 weeks suggests an alternative diagnosis, such as chronic inflammatory demyelinating polyneuropathy (CIDP). Cerebrospinal fluid protein usually rises during the second week of illness, without pleocytosis (albuminocytologic dissociation). The presence of CSF pleocytosis is not incompatible with GBS, but if it is significant (>50 cells), other diagnoses, particularly infection with the human immunodeficiency virus (HIV), should be suspected. The frequency of various GBS manifestations is shown in Table C23-2.

Table C23-2 Frequency of Features and Clinical Variants of Acute Guillain-Barré Syndrome

	Frequency (%)
Condition	Initially	In Fully Developed Illness
*Features of Syndrome*
Paresthesias	70	85
Weakness
Arms	20	90
Legs	60	95
Face	35	60
Oropharynx	25	50
Ophthalmoparesis	5	15
Sphincter dysfunction	15	5
Ataxia	10	15
Areflexia	75	90
Pain	25	30
Sensory loss	40	75
Respiratory failure	10	30
CSF protein >0.55 g/L	50	90
Abnormal electrophysiologic findings	95	99
*Clinical variants^
Fisher syndrome		5
Weakness without paresthesias or sensory loss		3
Pharyngeal-cervical-brachial weakness		3
Paraparesis		2
Facial paresis with paresthesias		1
Pure ataxia		1

* Variants are associated with diminished reflexes, demyelinating features as detected on electrophysiologic studies, and elevated cerebrospinal concentrations of fluid protein. Frequencies shown are those found in fully developed illness.

From Ropper AH. The Guillain-Barré syndrome. N Engl J Med 1992;326:1130–1136, with permission.

Because of its similarity to its animal analogue, experimental allergic neuritis, GBS was considered to be a single disorder characterized by an acute immune attack on myelin, hence the term acute inflammatory demyelinating polyneuropathy (AIDP). As the name implies, AIDP is characterized by prominent demyelination and inflammatory infiltrates in the spinal roots and nerves. Criteria for the diagnosis of GBS are based on the AIDP prototype and include both clinical and laboratory findings (Table C23-3). Until recently, AIDP had been used interchangeably with GBS. However, it is now well recognized that axonal forms of GBS exist. Several studies during the last two decades have documented that, although most cases of GBS are characterized by segmental demyelination, many patients with typical GBS have evidence of primary axonal degeneration (“axonal” GBS). GBS may be due to a pure motor axonopathy, named acute motor axonal neuropathy (AMAN), or a mixed sensorimotor axonopathies, named acute motor sensory axonal neuropathy (AMSAN) (Table C23-4). In addition to their electrophysiologic characteristics, the subtypes of GBS have characteristic pathological findings, with evidence of vesicular demyelination in AIDP and axonal phagocytosis in AMAN and AMSAN. Also, there is a strong association between GBS, particularly the AMAN form, with a preceding Campylobacter jejuni infection and the presence of serum antibodies directed toward ganglioside M1 (anti-GM1).

Table C23-3 Diagnostic Criteria for Guillain-Barré Syndrome (Mainly Acute Inflammatory Demyelinating Polyradiculoneuropathy)

Features Required for Diagnosis

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Aug 12, 2016 | Posted by admin in CARDIOLOGY | Comments Off

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